scholarly journals Ciliary photoreceptors in sea urchin larvae indicate pan-deuterostome cell type conservation

2019 ◽  
Author(s):  
Jonathan E. Valencia ◽  
Roberto Feuda ◽  
Dan O. Mellott ◽  
Robert D. Burke ◽  
Isabelle S. Peter
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Sea Urchin ◽  
Cell Types ◽  
Pigment Cells ◽  
Current Evidence ◽  
Regulatory State ◽  
Developmental Context ◽  
Immotile Cilia ◽  
Retinal Determination

ABSTRACTOne of the signatures of evolutionarily related cell types is the expression of similar combinations of transcription factors in distantly related animals. Here we present evidence that sea urchin larvae possess bilateral clusters of ciliary photoreceptors that are positioned in the oral/anterior apical neurogenic domain and associated with pigment cells. The expression of synaptotagmin indicates that the photoreceptors are neurons. Immunostaining shows that the sea urchin photoreceptors express an RGR/GO-opsin, opsin3.2, which co-localizes with tubulin on immotile cilia on the cell surface. Furthermore, orthologs of several transcription factors expressed in vertebrate photoreceptors are expressed in sea urchin ciliary photoreceptors, including Otx, Six3, Tbx2/3, and Rx, a transcription factor typically associated with ciliary photoreceptors. Analysis of gene expression during sea urchin development indicates that the photoreceptors derive from the anterior apical neurogenic domain. Thus, based on location, developmental origin, and transcription factor expression, sea urchin ciliary photoreceptors are likely homologous to vertebrate rods and cones. However, we found that genes typically involved in eye development in many animals, including pax6, six1/2, eya, and dac, are not expressed in sea urchin ciliary photoreceptors. Instead, all four genes are co-expressed in the hydropore canal, indicating that these genes operate as a module in an unrelated developmental context. Thus, based on current evidence, we conclude that at least within deuterostomes, ciliary photoreceptors share a common evolutionary origin and express a shared regulatory state that includes Rx, Otx, and Six3, but not transcription factors that are commonly associated with the retinal determination circuit.

scholarly journals Ciliary photoreceptors in sea urchin larvae indicate pan-deuterostome cell type conservation

BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Jonathan E. Valencia ◽  
Roberto Feuda ◽  
Dan O. Mellott ◽  
Robert D. Burke ◽  
Isabelle S. Peter
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Sea Urchin ◽  
Evolutionary Relationship ◽  
Cell Types ◽  
Developmental Expression ◽  
Pigment Cells ◽  
Cell Type ◽  
Neuronal Marker ◽  
Neurogenic Ectoderm

Abstract Background The evolutionary history of cell types provides insights into how morphological and functional complexity arose during animal evolution. Photoreceptor cell types are particularly broadly distributed throughout Bilateria; however, their evolutionary relationship is so far unresolved. Previous studies indicate that ciliary photoreceptors are homologous at least within chordates, and here, we present evidence that a related form of this cell type is also present in echinoderm larvae. Results Larvae of the purple sea urchin Strongylocentrotus purpuratus have photoreceptors that are positioned bilaterally in the oral/anterior apical neurogenic ectoderm. Here, we show that these photoreceptors express the transcription factor Rx, which is commonly expressed in ciliary photoreceptors, together with an atypical opsin of the GO family, opsin3.2, which localizes in particular to the cilia on the cell surface of photoreceptors. We show that these ciliary photoreceptors express the neuronal marker synaptotagmin and are located in proximity to pigment cells. Furthermore, we systematically identified additional transcription factors expressed in these larval photoreceptors and found that a majority are orthologous to transcription factors expressed in vertebrate ciliary photoreceptors, including Otx, Six3, Tbx2/3, and Rx. Based on the developmental expression of rx, these photoreceptors derive from the anterior apical neurogenic ectoderm. However, genes typically involved in eye development in bilateria, including pax6, six1/2, eya, and dac, are not expressed in sea urchin larval photoreceptors but are instead co-expressed in the hydropore canal. Conclusions Based on transcription factor expression, location, and developmental origin, we conclude that the sea urchin larval photoreceptors constitute a cell type that is likely homologous to the ciliary photoreceptors present in chordates.

scholarly journals HOT or not: examining the basis of high-occupancy target regions

2017 ◽  
Author(s):  
Katarzyna Wreczycka ◽  
Vedran Franke ◽  
Bora Uyar ◽  
Ricardo Wurmus ◽  
Altuna Akalin
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Binding Sites ◽  
Cell Types ◽  
Data Sets ◽  
Gene Promoters ◽  
Quadruplex Dna ◽  
Golden Standard ◽  
Multiple Cell ◽  
Multiple Species

AbstractHigh-occupancy target (HOT) regions are the segments of the genome with unusually high number of transcription factor binding sites. These regions are observed in multiple species and thought to have biological importance due to high transcription factor occupancy. Furthermore, they coincide with house-keeping gene promoters and the associated genes are stably expressed across multiple cell types. Despite these features, HOT regions are solemnly defined using ChIP-seq experiments and shown to lack canonical motifs for transcription factors that are thought to be bound there. Although, ChIP-seq experiments are the golden standard for finding genome-wide binding sites of a protein, they are not noise free. Here, we show that HOT regions are likely to be ChIP-seq artifacts and they are similar to previously proposed “hyper-ChIPable” regions. Using ChIP-seq data sets for knocked-out transcription factors, we demonstrate presence of false positive signals on HOT regions. We observe sequence characteristics and genomic features that are discriminatory of HOT regions, such as GC/CpG-rich k-mers and enrichment of RNA-DNA hybrids (R-loops) and DNA tertiary structures (G-quadruplex DNA). The artificial ChIP-seq enrichment on HOT regions could be associated to these discriminatory features. Furthermore, we propose strategies to deal with such artifacts for the future ChIP-seq studies.

scholarly journals Virtual ChIP-seq: predicting transcription factor binding by learning from the transcriptome

2018 ◽  
Author(s):  
Mehran Karimzadeh ◽  
Michael M. Hoffman
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Binding Sites ◽  
Cell Types ◽  
Transcription Factor Binding ◽  
Regulatory Function ◽  
Factor Binding ◽  
Link Type ◽  
Genomic Regions ◽  
Factor Sequence

AbstractMotivationIdentifying transcription factor binding sites is the first step in pinpointing non-coding mutations that disrupt the regulatory function of transcription factors and promote disease. ChIP-seq is the most common method for identifying binding sites, but performing it on patient samples is hampered by the amount of available biological material and the cost of the experiment. Existing methods for computational prediction of regulatory elements primarily predict binding in genomic regions with sequence similarity to known transcription factor sequence preferences. This has limited efficacy since most binding sites do not resemble known transcription factor sequence motifs, and many transcription factors are not even sequence-specific.ResultsWe developed Virtual ChIP-seq, which predicts binding of individual transcription factors in new cell types using an artificial neural network that integrates ChIP-seq results from other cell types and chromatin accessibility data in the new cell type. Virtual ChIP-seq also uses learned associations between gene expression and transcription factor binding at specific genomic regions. This approach outperforms methods that predict TF binding solely based on sequence preference, pre-dicting binding for 36 transcription factors (Matthews correlation coefficient > 0.3).AvailabilityThe datasets we used for training and validation are available at https://virchip.hoffmanlab.org. We have deposited in Zenodo the current version of our software (http://doi.org/10.5281/zenodo.1066928), datasets (http://doi.org/10.5281/zenodo.823297), predictions for 36 transcription factors on Roadmap Epigenomics cell types (http://doi.org/10.5281/zenodo.1455759), and predictions in Cistrome as well as ENCODE-DREAM in vivo TF Binding Site Prediction Challenge (http://doi.org/10.5281/zenodo.1209308).

scholarly journals An Algorithm for Cellular Reprogramming

2017 ◽  
Author(s):  
Scott Ronquist ◽  
Geoff Patterson ◽  
Markus Brown ◽  
Stephen Lindsly ◽  
Haiming Chen ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Cell Biology ◽  
Human Fibroblasts ◽  
Cell Types ◽  
Approximate Model ◽  
Cellular Reprogramming ◽  
Biological Processes ◽  
Moderate Complexity

AbstractThe day we understand the time evolution of subcellular elements at a level of detail comparable to physical systems governed by Newton’s laws of motion seems far away. Even so, quantitative approaches to cellular dynamics add to our understanding of cell biology, providing data-guided frameworks that allow us to develop better predictions about, and methods for, control over specific biological processes and system-wide cell behavior. In this paper, we describe an approach to optimizing the use of transcription factors (TFs) in the context of cellular reprogramming. We construct an approximate model for the natural evolution of a cell cycle synchronized population of human fibroblasts, based on data obtained by sampling the expression of 22,083 genes at several time points along the cell cycle. In order to arrive at a model of moderate complexity, we cluster gene expression based on the division of the genome into topologically associating domains (TADs) and then model the dynamics of the TAD expression levels. Based on this dynamical model and known bioinformatics, such as transcription factor binding sites (TFBS) and functions, we develop a methodology for identifying the top transcription factor candidates for a specific cellular reprogramming task. The approach used is based on a device commonly used in optimal control. Our data-guided methodology identifies a number of transcription factors previously validated for reprogramming and/or natural differentiation. Our findings highlight the immense potential of dynamical models, mathematics, and data-guided methodologies for improving strategies for control over biological processes.Significance StatementReprogramming the human genome toward any desirable state is within reach; application of select transcription factors drives cell types toward different lineages in many settings. We introduce the concept of data-guided control in building a universal algorithm for directly reprogramming any human cell type into any other type. Our algorithm is based on time series genome transcription and architecture data and known regulatory activities of transcription factors, with natural dimension reduction using genome architectural features. Our algorithm predicts known reprogramming factors, top candidates for new settings, and ideal timing for application of transcription factors. This framework can be used to develop strategies for tissue regeneration, cancer cell reprogramming, and control of dynamical systems beyond cell biology.

scholarly journals Direct reprogramming of human fibroblasts into insulin-producing cells by transcription factors

2021 ◽  
Author(s):  
Rosa Gasa ◽  
Marta Fontcuberta-PiSunyer ◽  
Ainhoa García-Alamán ◽  
Élia Prades ◽  
Noèlia Téllez ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Somatic Cell ◽  
Human Fibroblasts ◽  
Stem Cell Differentiation ◽  
Cell Types ◽  
Skin Fibroblasts ◽  
Direct Reprogramming ◽  
Β Cell ◽  
Insulin Producing Cells

Direct lineage reprogramming of one somatic cell into another bypassing an intermediate pluripotent state has emerged as an alternative to embryonic or induced pluripotent stem cell differentiation to generate clinically relevant cell types. One cell type of clinical interest is the pancreatic β cell that secretes insulin and whose loss and/or dysfunction leads to diabetes. Generation of functional β-like cells from developmentally related somatic cell types (pancreas, liver, gut) has been achieved via enforced expression of defined sets of transcription factors. However, clinical applicability of these findings is challenging because the starting cell types are not easily obtainable. Skin fibroblasts are accessible and easily manipulated cells that could be a better option, but available studies indicate that their competence to give rise to β cells through similar direct reprogramming approaches is limited. Here, using human skin fibroblasts and a protocol that ensures high and consistent expression of adenovirus-encoded reprogramming factors, we show that the transcription factor cocktail consisting of Pdx1, Ngn3, MafA, Pax4 and Nkx2-2 activates key β cell genes and down-regulates the fibroblast transcriptional program. The converted cells produce insulin and exhibit intracellular calcium responses to glucose and/or membrane depolarization. Furthermore, they secrete insulin in response to glucose in vitro and after transplantation in vivo. These findings demonstrate that transcription factor-mediated direct reprogramming of human fibroblasts is a feasible strategy to generate insulin-producing cells.

scholarly journals Ratio-based sensing of two transcription factors regulates the transit to differentiation

2018 ◽  
Author(s):  
Sebastian M. Bernasek ◽  
Jean-François Boisclair Lachance ◽  
Nicolás Peláez ◽  
Rachael Bakker ◽  
Heliodoro Tejedor Navarro ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Progenitor Cells ◽  
Cell Fate ◽  
Statistical Physics ◽  
Gene Dosage ◽  
State Transitions ◽  
Developmental Context ◽  
The Absolute

ABSTRACTCells must reliably respond to changes in transcription factor levels in order to execute cell state transitions in the correct time and place. These transitions are typically thought to be triggered by changes in the absolute nuclear concentrations of relevant transcription factors. We have identified a developmental context in which cell fate transitions depend on changes in the relative concentrations of two transcription factors. Here, we quantify the in vivo expression dynamics of Yan and Pointed, two essential E-twenty-six (ETS) proteins that regulate transcription during eye development in Drosophila. These two factors exert opposing influences; one impedes transcription of gene targets required for differentiation while the other promotes it. We show that both proteins are transiently co-expressed in eye progenitor cells and also during photoreceptor specification. To decide whether to undergo state transitions, cells respond to the ratio of the two protein concentrations rather than changes in the absolute abundance of either transcription factor. We show that a simple model based on the statistical physics of protein-DNA binding illustrates how this ratiometric sensing of transcription factor concentrations could occur. Gene dosage experiments reveal that progenitor cells stabilize the ratio against fluctuations in the absolute concentration of either protein. We further show that signaling inputs via the Notch and Receptor Tyrosine Kinase (RTK) pathways set the ratio in progenitor cells, priming them for either transit to differentiation or for continued multipotency. A sustained change in the ratio accompanies the transit to differentiation This novel mechanism allows for distributed control of developmental transitions by multiple transcription factors, making the system robust to fluctuating genetic or environmental conditions.

scholarly journals Transcriptional Regulation of Autophagy Genes via Stage-Specific Activation of CEBPB and PPARG during Adipogenesis: A Systematic Study Using Public Gene Expression and Transcription Factor Binding Datasets

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1321 ◽  
Author(s):  
Mahmoud Ahmed ◽  
Trang Huyen Lai ◽  
Jin Seok Hwang ◽  
Sahib Zada ◽  
Trang Minh Pham ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Transcriptional Regulation ◽  
Transcription Factors ◽  
High Throughput Sequencing ◽  
Cell Model ◽  
Cell Types ◽  
Autophagy Gene ◽  
Occupancy Patterns ◽  
Differentiation Stage

Autophagy is the cell self-eating mechanism to maintain cell homeostasis by removing damaged intracellular proteins or organelles. It has also been implicated in the development and differentiation of various cell types including the adipocyte. Several links between adipogenic transcription factors and key autophagy genes has been suggested. In this study, we tried to model the gene expression and their transcriptional regulation during the adipocyte differentiation using high-throughput sequencing datasets of the 3T3-L1 cell model. We applied the gene expression and co-expression analysis to all and the subset of autophagy genes to study the binding, and occupancy patterns of adipogenic factors, co-factors and histone modifications on key autophagy genes. We also analyzed the gene expression of key autophagy genes under different transcription factor knockdown adipocyte cells. We found that a significant percent of the variance in the autophagy gene expression is explained by the differentiation stage of the cell. Adipogenic master regulators, such as CEBPB and PPARG target key autophagy genes directly. In addition, the same factor may also control autophagy gene expression indirectly through autophagy transcription factors such as FOXO1, TFEB or XBP1. Finally, the binding of adipogenic factors is associated with certain patterns of co-factors binding that might modulate the functions. Some of the findings were further confirmed under the knockdown of the adipogenic factors in the differentiating adipocytes. In conclusion, autophagy genes are regulated as part of the transcriptional programs through adipogenic factors either directly or indirectly through autophagy transcription factors during adipogenesis.

Pattern formation during gastrulation in the sea urchin embryo

Development ◽  
1992 ◽  
Vol 116 (Supplement) ◽  
pp. 33-41 ◽  
Author(s):  
David R. McClay ◽  
Norris A. Armstrong ◽  
Jeff Hardin
Keyword(s):  
Sea Urchin ◽  
Spatial Information ◽  
Cell Types ◽  
Cell Interactions ◽  
Pigment Cells ◽  
Original Position ◽  
Embryonic Cells ◽  
Sea Urchin Embryo ◽  
Mesenchyme Cells ◽  
Primary Mesenchyme Cells

The sea urchin embryo follows a relatively simple cell behavioral sequence in its gastrulation movements. To form the mesoderm, primary mesenchyme cells ingress from the vegetal plate and then migrate along the basal lamina lining the blastocoel. The presumptive secondary mesenchyme and endoderm then invaginate from the vegetal pole of the embryo. The archenteron elongates and extends across the blastocoel until the tip of the archenteron touches and attaches to the opposite side of the blastocoel. Secondary mesenchyme cells, originally at the tip of the archenteron, differentiate to form a variety of structures including coelomic pouches, esophageai muscles, pigment cells and other cell types. After migration of the secondary mesenchyme cells from their original position at the tip of the archenteron, the endoderm fuses with an invagination of the ventral ectoderm (the stomodaem), to form the mouth and complete the process of gastrulation. A larval skeleton is made by primary mesenchyme cells during the time of archenteron and mouth formation. A number of experiments have established that these morphogenetic movements involve a number of cell autonomous behaviors plus a series of cell interactions that provide spatial, temporal and scalar information to cells of the mesoderm and endoderm. The cell autonomous behaviors can be demonstrated by the ability of micromeres or endoderm to perform their morphogenetic functions if either is isolated and grown in culture. The requirement for cell interactions has been demonstrated by manipulative experiments where it has been shown that axial information, temporal information, spatial information and scalar information is obtained by mesoderm and endoderm from other embryonic cells. This information governs the cell autonomous behavior and places the cells in the correct embryonic context.

scholarly journals Macromere cell fates during sea urchin development

Development ◽  
1991 ◽  
Vol 113 (4) ◽  
pp. 1085-1091 ◽  
Author(s):  
R.A. Cameron ◽  
S.E. Fraser ◽  
R.J. Britten ◽  
E.H. Davidson
Keyword(s):  
Sea Urchin ◽  
Pigment Cell ◽  
Cell Lineage ◽  
Cell Types ◽  
Cellular Migration ◽  
The Other ◽  
Pigment Cells ◽  
Basal Cells ◽  
Cell Fates ◽  
Gut Pigment

This paper examines the cell lineage relationships and cell fates in embryos of the sea urchin Strongylocentrotus purpuratus leading to the various cell types derived from the definitive vegetal plate territory or the veg2 tier of cells. These cell types are gut, pigment cells, basal cells and coelomic pouches. They are cell types that constitute embryonic structures through cellular migration or rearrangement unlike the relatively non-motile ectoderm cell types. For this analysis, we use previous knowledge of lineage to assign macromeres to one of four types: VOM, the oral macromere; VAM, the aboral macromere, right and left VLM, the lateral macromeres. Each of the four macromeres contributes progeny to all of the cell types that descend from the definitive vegetal plate. Thus in the gut each macromere contributes to the esophagus, stomach and intestine, and the stripe of labeled cells descendant from a macromere reflects the re-arrangement of cells that occurs during archenteron elongation. Pigment cell contributions exhibit no consistent pattern among the four macromeres, and are haphazardly distributed throughout the ectoderm. Gut and pigment cell contributions are thus radially symmetrical. In contrast, the VOM blastomere contributes to both of the coelomic pouches while the other three macromeres contribute to only one or the other pouch. The total of the macromere contribution amounts to 60% of the cells constituting the coelomic pouches.

scholarly journals Identification ofkit-ligand aas the Gene Responsible for the Medaka Pigment Cell Mutantfew melanophore

2019 ◽  
Author(s):  
Yuji Otsuki ◽  
Yuki Okuda ◽  
Kiyoshi Naruse ◽  
Hideyuki Saya
Keyword(s):  
Transcription Factors ◽  
Pigment Cell ◽  
Cell Types ◽  
The Body ◽  
Pigment Cells ◽  
Cell Specification ◽  
Kit Ligand ◽  
Body Coloration ◽  
Insight Into ◽  
Pigmentation Disorders

ABSTRACTThe body coloration of animals is due to pigment cells derived from neural crest cells, which are multipotent and differentiate into diverse cell types. Medaka (Oryzias latipes) possesses four distinct types of pigment cells known as melanophores, xanthophores, iridophores, and leucophores. Thefew melanophore(fm) mutant of medaka is characterized by reduced numbers of melanophores and leucophores. We here identifykit-ligand a(kitlga) as the gene whose mutation gives rise to thefmphenotype. This identification was confirmed by generation ofkitlgaknockout medaka and the findings that these fish also manifest reduced numbers of melanophores and leucophores and fail to rescue thefmmutant phenotype. We also found that expression ofsox5,pax7a,pax3a, andmitfagenes is down-regulated in bothfmandkitlgaknockout medaka, implicating c-Kit signaling in regulation of the expression of these genes as well as the encoded transcription factors in pigment cell specification. Our results may provide insight into the pathogenesis of c-Kit–related pigmentation disorders such as piebaldism in humans, and ourkitlgaknockout medaka may prove useful as a tool for drug screening.

Sign in / Sign up

Export Citation Format

Share Document